Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D00446 (Sucralfate)
 278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 micrograms/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid-suppressive agent. Prior to the study of combined EGF and sucralfate, oral sucralfate was confirmed to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of epidermal growth factor in combination with sucralfate or omeprazole on the healing of chronic gastric ulcers in the rat. 221 45

Gastric emptying studies were performed on nine healthy volunteers and ten duodenal ulcer (DU) patients utilizing a dual radionuclide technique to assess simultaneously emptying rates of liquid (111In labeled water) and solid (99mTc sulfur colloid labeled chicken liver) components of a meal. One gram of sucralfate was compared to placebo in separate days in a randomized double-blind crossover fashion. Subjects ingested the radiolabeled test meal 1 h after receiving medication, and gastric emptying was monitored for 3 h using a gamma camera interfaced with a computer. We found that DU patients had significantly faster gastric emptying of solids (P less than 0.05) compared to normals on the placebo days, while liquid emptying rates were similar. Sucralfate, in the DU patients, significantly (P less than 0.05) slowed gastric emptying of water from 20 to 40 min and emptying of the solid component from 100-160 min after the meal compared to placebo. In normal subjects, gastric emptying of liquids and solids was not significantly affected by sucralfate. We conclude that slowing of gastric emptying, possibly mediated through aluminum ions, occurs in DU patients on sucralfate. This may be one mechanism by which sucralfate enhances healing and decreases recurrence of duodenal ulcer.
 ...
PMID:Sucralfate delays gastric emptying of liquids and solids in duodenal ulcer patients. 277 80

The first part of the study consisted of 110 rats in 11 groups with ten rats in each. Nine of the groups were fed nutrient solutions of different compositions, antacid and sucralfate through orogastric tube during induction of stress ulcer by restraint and a cold ambient temperature. One group served as a control group and received no feeding and the 11th group was given cimetidine intraperitoneally. The extensiveness of the stress effect was estimated in each group by the number of rats with ulcer as percentage, the mean number of ulcers in each rat, the mean distribution of ulcers of different sizes, the mean total of mucosal damage in each rat and the contribution of ulcers of a different size to the total mucosal damage. The results showed that cimetidine is an effective protector against stress ulcer. Guar gum, Intralipid (fat emulsion), egg protein and 30 per cent glucose are slightly weaker protectors than cimetidine but much stronger than 10 per cent glucose wheat flour and distilled water. Sucralfate increased the susceptibility to stress ulcer. The second part of the study consisted of 86 rats. It showed, that guar gum increased the healing rate of stress ulcers. During a 30 hour treatment period after four hours of stress, the rats fed guar gum (n = 30) showed a lower (p less than 0.001) number of ulcers than the control rats fed normal rat food (n = 26) or immediately after the four hours of stress (n = 30). The mechanisms suggested for ulcer prevention and increased ulcer healing rate found herein may be due to reduced acidity, increased local mucosal supply of energy and mechanical protection.
 ...
PMID:The protective effect of nutrients against stress induced gastric ulcers in the rat. 282 67

Syrup of ipecac (SOI) is a commonly used emetic for toxic ingestions. A preliminary study was undertaken to quantify the efficacy of SOI-induced emesis. Three groups of adult subjects fasted overnight before ingestion of 1 mCi of Tc-99m human serum albumin-sucralfate. Sucralfate is minimally absorbed from the gastrointestinal tract and has a gastric clearance half-time of 90 minutes, approximately equal to that of solid foods. At 5, 30, and 60 minutes after ingestion of radiolabeled sucralfate (RSC), subjects were given a standard dose of 30 ml SOI and 240 ml of water. Gastrointestinal tract images were obtained both at the time of ingestion of RSC and 60 minutes after ingestion of SOI. Regions-of-interest were drawn and activity measured over the stomach and small bowel with correction for physical decay. Those subjects (N = 10) treated at 5 minutes after ingestion retained a mean value of 17% of the administered RSC by 60 minutes. The group (N = 5) treated at 30 minutes after ingestion retained a mean value of 41%, while those (N = 5) treated at 60 minutes retained a mean value of 56%. The results tend to confirm the efficacy of SOI-induced emesis when SOI is given promptly (i.e., 5 minutes) following ingestion, and generally support efforts to assure widespread immediate availability of SOI for toxic ingestions.
 ...
PMID:Efficacy of syrup of ipecac-induced emesis for emptying gastric contents. 290 46

We have validated a method to measure bile salt binding by Maalox (aluminum hydroxide and magnesium hydroxide), Carafate (sucralfate), and Questran (cholestyramine) in vitro. The method used in this study involves a correction for adherent water volume and thus provides a correct measure of bile salt binding. With this approach, we described the binding properties of Maalox, Carafate, and Questran. The bile salt binding capacities of Carafate and Maalox are limited and do not have physiological or pharmacological significance. On the other hand, we found that Questran has substantial bile salt binding capacity. At the recommended dosage, Questran could deplete the total bile salt pool. We also found that Carafate, although not used as an antacid, has buffering capacity (maintaining a pH of solution in the range 4.2-4.8) which might contribute to its effectiveness as an ulcer treatment drug.
 ...
PMID:Bile salt binding properties of commonly used gastrointestinal drugs: maalox, carafate, and questran. 317 34

A large number of pharmacokinetic studies have been carried out using 4-quinolones in order to estimate total and renal clearance, to examine tissue penetration, to establish suitable dosage regimens and to determine the influence of kidney and liver impairment on the pharmacokinetic behaviour. Although the quinolones are poorly water soluble over the physiological pH range (6-8) they are well absorbed following oral administration. Ofloxacin is almost completely absorbed and ciprofloxacin has been shown to have an absolute bioavailability of 0.70. Plasma protein binding varies greatly from quinolone to quinolone ranging from about 10% in the case of norfloxacin to more than 90% in the case of nalidixic acid. Penetration of the quinolones into the prostate is generally good. Most quinolones, too, have been shown to penetrate blister fluid rapidly and this model has proved useful in distribution studies. Some quinolones, like ofloxacin, are excreted largely unchanged while others like pefloxacin and acrosoxacin, are almost completely metabolized. Conjugation to very water-soluble glucuronides is not common although other types of metabolites have been shown. Little information appears to have been published on the effect of liver disease on the metabolism of the quinolones. This must be an important consideration for this type of drugs which are subject to hepatic transformation. The pharmacokinetic behaviour of quinolones in patients with impaired renal function has been extensively studied. The interaction of food on the absorption does not seem to be great, there is however evidence of a drug interaction between theophylline and some of the newer quinolones. Sucralfate and antacids containing Mg2+ or (and) Al3+-ions can markedly impair the absorption of quinolone antibiotics.
 ...
PMID:Pharmacokinetics of the newer fluoroquinolones. 332 26

Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg X day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0-5, and to obtain biopsy specimens for determination of mucosal prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha. Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.
 ...
PMID:Gastric protection by sucralfate. Role of mucus and prostaglandins. 346 Sep 26

Sucralfate, an agent that heals peptic ulcers in humans, has been shown to reduce aspirin-induced gastric mucosal damage in experimental animals. It has been suggested that the protective effect of sucralfate is due to stimulation of local prostaglandin production. The purpose of this study was to establish whether sucralfate was capable of reducing aspirin-induced gastric damage in humans. The effect of 1 g of sucralfate or identical placebo was studied in random order in eight healthy subjects. To determine if the effect of sucralfate was related to local prostaglandin synthesis, a second series of studies was performed in which prostaglandin production was inhibited with indomethacin 50 mg given orally eight hours before sucralfate. In each subject, all studies were performed at least one week apart. Following an overnight fast, upper gastrointestinal endoscopy was performed, with sucralfate or placebo given orally 30 minutes before ingestion of 1,200 mg of soluble aspirin in 50 ml of water. Both endoscopist and subject were unaware of the test agent. Ninety minutes after aspirin ingestion, endoscopy was again performed and gastric mucosal lesions were counted and graded to derive an erosion score. Results are expressed as mean +/- SEM. Aspirin produced endoscopic changes (score of 2.75 +/- 0.49) that were significantly (p less than 0.05) inhibited by sucralfate (score of 1.13 +/- 0.44). The protective effect of sucralfate was abolished by pretreatment with indomethacin (scores of 2.88 +/- 0.55 and 1.88 +/- 0.40, respectively). These results demonstrate that sucralfate significantly protects the human gastric mucosa against the acute damaging effects of aspirin. This effect is abolished by indomethacin, suggesting that the protective action of sucralfate on the gastric mucosa of humans may be related to stimulation of endogenous prostaglandins.
 ...
PMID:Protective effect of sucralfate against aspirin-induced damage to the human gastric mucosa. 366 13

The effects of oral sucralfate, a basic aluminum salt of sulfated disaccharide, on various experimental gastric lesions and on gastric secretion were studied in rats. Sucralfate at 300 mg/kg potently inhibited the development of Shay ulcers and indomethacin- and aspirin-induced erosions. The drug at 1000 mg/kg also potently inhibited histamine-induced erosions. Water-immersion stress-induced erosions were inhibited with 1000 mg/kg of the drug, but the degree of inhibition was weaker than that seen in other types of erosion formation. Sucralfate at 1000 mg/kg given twice daily for 14 days significantly accelerated the spontaneous healing of acetic acid-induced ulcers. Sucralfate at over 300 mg/kg tended to increase the volume of gastric juice but had an insignificant effect on acid and pepsin output of pylorus-ligated rats. As a whole, the effects of sucralfate on experimental gastric lesions appear to be much more potent than Maalox, propantheline bromide, and cimetidine. The mechanism of action of sucralfate remains to be determined.
 ...
PMID:Effects of an antiulcer drug, sucralfate (a basic aluminum salt of sulfated disaccharide), on experimental gastric lesions and gastric secretion in rats. 668 79

Absorption of ketoconazole is impaired in subjects with an increased gastric pH due to administration of antacids, H2-receptor antagonists, proton pump inhibitors, or the presence of hypochlorhydria. Sucralfate could provide an attractive alternative in patients receiving ketoconazole who require therapy for acid-peptic disorders. Twelve healthy human volunteers were administered a single 400-mg oral dose of ketoconazole in each of three randomized treatment phases. In phase A, ketoconazole was administered orally with 240 ml of water. In phase B, ketoconazole and sucralfate (1.0 g) were administered simultaneously with 240 ml of water. In phase C, ketoconazole was administered with 240 ml of water 2 h after administration of sucralfate (1.0 g) orally with 240 ml of water. A 680-mg oral dose of glutamic acid hydrochloride was administered 10 min prior to and with each dose of ketoconazole, sucralfate, or ketoconazole plus sucralfate. Simultaneous administration of ketoconazole and sucralfate led to a significant reduction in the area under the concentration-time curve and maximal concentration of ketoconazole in serum (78.12 +/- 12.20 versus 59.32 +/- 13.61 micrograms.h/ml and 12.34 +/- 3.07 versus 8.92 +/- 2.57 micrograms/ml, respectively; P < 0.05). When ketoconazole was administered 2 h after sucralfate, the observed ketoconazole area under the concentration-time curve was not significantly decreased compared with that of ketoconazole alone. The time to maximal concentrations in serum and the ketoconazole elimination rate constant were not significantly different in any of the three treatment phases. In patients receiving concurrent administration of ketoconazole and sucralfate, doses should be separated by at least 2 h.
 ...
PMID:In vivo interaction of ketoconazole and sucralfate in healthy volunteers. 791 Jul 24


1 2 Next >>